Toxicity of L-proline toward rat hippocampal neurons

Intrahippocampal injections of L-proline, a neutral amino acid excitant, non-selectively destroyed pyramidal and granule cells. Co-administration of equimolar kynurenate, an excitatory amino acid antagonist, markedly reduced the extent of neuronal cell death. L-Proline destroyed far more hippocampal neurons than D-proline, in keeping with its greater neuroexcitatory potency. L-Proline must therefore be added to the list of excitotoxins present in brain. Its excitotoxic action may be related to the neurological and cognitive deficits associated with hyperprolinemia.